Differential roles of epigenetic changes and Foxp3 expression in regulatory T cell-specific transcriptional regulation
Hiromasa Morikawa(Kyoto University), Naganari Ohkura, Alexis Vandenbon(Osaka International University), Masayoshi Itoh(RIKEN), Sayaka Nagao-Sato(RIKEN Center for Integrative Medical Sciences), Hideya Kawaji(RIKEN), Timo Lassmann(RIKEN Center for Integrative Medical Sciences), Piero Carninci(RIKEN Center for Integrative Medical Sciences), Yoshihide Hayashizaki(RIKEN), Alistair R. R. Forrest(RIKEN Center for Integrative Medical Sciences), Daron M. Standley(Osaka International University), Hiroshi Date(Kyoto University), Shimon Sakaguchi(Japan Science and Technology Agency), Alistair R. R. Forrest(RIKEN Center for Integrative Medical Sciences), Hideya Kawaji(RIKEN), Michael Rehli, J. Kenneth Baillie, Michiel de Hoon, Vanja Haberle, Timo Lassmann(RIKEN Center for Integrative Medical Sciences), Ivan V. Kulakovskiy, Marina Lizio, Masayoshi Itoh(RIKEN), Robin Andersson, Chris Mungall, Terrence F. Meehan, Sebastian Schmeier, Nicolas Bertin, Mette Jørgensen, Emmanuel Dimont, Erik Arner, Christian Schmidl, Ulf Schaefer, Yulia A. Medvedeva, Charles Plessy, Morana Vitezic, Jessica Severin, Colin A. Semple, Yuri Ishizu, Margherita Francescatto, Intikhab Alam, Davide Albanese, Gabriel Altschuler, John A. C. Archer, Peter Arner, Magda Babina, Sarah Baker, Piotr J. Balwierz, Anthony G Beckhouse, Swati Pradhan-Bhatt, Judith A. Blake, Antje Blumenthal, Beatrice Bodega, Alessandro Bonetti, James Briggs, Frank Brombacher, A. Maxwell Burroughs, Andrea Califano, Carlo Vittorio Cannistraci, Daniel Carbajo, Yun Chen, Marco Chierici, Yari Ciani, Hans Clevers, Emiliano Dalla, Carrie Davis, Bart Deplancke, Michael Detmar, Alexander D. Diehl, Taeko Dohi, Finn Drabløs, Albert S.B. Edge, Matthias Edinger, Karl Ekwall, Mitsuhiro Endoh, Hideki Enomoto, Michela Fagiolini, Lynsey Fairbairn, Hai Fang, Mary C. Farach‐Carson, Geoffrey J. Faulkner, Alexander V. Favorov, Malcolm E Fisher, Martin C. Frith, Rie Fujita, Shiro Fukuda, Cesare Furlanello, Masaaki Furuno, Jun-ichi Furusawa, Teunis B. H. Geijtenbeek, Andrew Gibson, T Gingeras, Dan Goldowitz, Julian Gough, Sven Guhl, Reto Guler, Stefano Gustincich, Thomas J Ha, Masahide Hamaguchi, Mitsuko Hara, Matthias Harbers, Jayson Harshbarger, Akira Hasegawa, Yuki Hasegawa, Takehiro Hashimoto, Meenhard Herlyn, Kelly J Hitchens, Shannan J. Ho Sui, Oliver Hofmann, Ilka Hoof, Fumi Hori, Łukasz Huminiecki, Kei Iida, Tomokatsu Ikawa(Osaka International University), Boris R. Janković, Hui Jia, Anagha Joshi, Giuseppe Jurman, Bogumił Kaczkowski, Chieko Kai, Kaoru Kaida, Ai Kaiho, Kazuhiro Kajiyama, Mutsumi Kanamori-Katayama, Artem S. Kasianov, Takeya Kasukawa, Shintaro Katayama, Sachi Kato, Shuji Kawaguchi, Hiroshi Kawamoto(Kyoto University), Yuki I. Kawamura, Tsugumi Kawashima, Judith S. Kempfle, Tony Kenna, Juha Kere, Levon M. Khachigian, Toshio Kitamura, S. Peter Klinken, Alan J. Knox, Miki Kojima, Soichi Kojima, Naoto Kondo, Haruhiko Koseki, Shigeo Koyasu, Sarah Krampitz, Atsutaka Kubosaki, Andrew Tae-Jun Kwon, Jeroen F. J. Laros, Weon-Ju Lee, Andreas Lennartsson, Kang Li, Berit Lilje, Leonard Lipovich, Alan Mackay‐Sim, Ri‐Ichiroh Manabe, Jessica C. Mar, Benoı̂t Marchand, Anthony Mathelier, Niklas Mejhert, Alison Meynert, Yosuke Mizuno, David Anderson de Lima Morais, Hiromasa Morikawa(Kyoto University), Mitsuru Morimoto, Kazuyo Moro, Efthymios Motakis, Hozumi Motohashi, Christine L. Mummery, Mitsuyoshi Murata, Sayaka Nagao-Sato(RIKEN Center for Integrative Medical Sciences), Yutaka Nakachi, Fumio Nakahara, Toshiyuki Nakamura, Yukio Nakamura, Kenichi Nakazato, Erik van Nimwegen, Noriko Ninomiya, Hiromi Nishiyori, Shohei Noma, Tadasuke Nozaki, Soichi Ogishima, Naganari Ohkura, Hiroko Ohmiya, Hiroshi Ohno(Kyoto University), Mitsuhiro Ohshima, Mariko Okada, Yasushi Okazaki, Valerio Orlando, Dmitry A. Ovchinnikov, Arnab Pain, Robert Passier, Margaret Patrikakis, Helena Persson, Silvano Piazza, James Prendergast, Owen J. L. Rackham, Jordan A. Ramilowski, Mamoon Rashid, Timothy Ravasi, Patrizia Rizzu, Marco Roncador, Sugata Roy, Morten Beck Rye, Eri Saijyo, Antti Sajantila, Akiko Saka, Shimon Sakaguchi(Japan Science and Technology Agency), Mizuho Sakai, Hiroki Sato, Hironori Satoh, Suzana Savvi, Alka Saxena, Claudio Schneider, Erik Schultes, Gundula Schulze‐Tanzil, Anita Schwegmann, Thierry Sengstag, Guojun Sheng, Hisashi Shimoji, Yishai Shimoni, Jay W. Shin, Christophe Simon, Daisuke Sugiyama, Takaaki Sugiyama, Masanori Suzuki, Rolf Swoboda, Peter A.C. ’t Hoen, Michihira Tagami, Takahashi Naoko, Jun Takai, Hiroshi Tanaka(Kyoto University), Hideki Tatsukawa, Zuotian Tatum, Mark Thompson, Hiroo Toyoda, Tetsuro Toyoda, Eivind Valen, Marc van de Wetering, Linda Berg, Roberto Verardo, Dipti Vijayan, Ilya E. Vorontsov, Wyeth W. Wasserman, Shoko Watanabe, Christine A. Wells, Louise N Winteringham, Ernst J. Wolvetang, Emily J. Wood, Yoko Yamaguchi, Masayuki Yamamoto, Misako Yoneda, Yohei Yonekura, Shigehiro Yoshida, Suzan E. Zabierowski, Peter Zhang, Xiaobei Zhao, S. Zucchelli, Kim Summers, Harukazu Suzuki, Carsten O. Daub, Jun Kawai, Peter Heutink, Winston Hide, Tom C. Freeman, Boris Lenhard, Vladimir B. Bajić, Martin S. Taylor, Vsevolod J. Makeev, Albin Sandelin, David Hume, Piero Carninci(RIKEN Center for Integrative Medical Sciences), Yoshihide Hayashizaki(RIKEN)
Cited by 138Open Access
Abstract
Naturally occurring regulatory T (Treg) cells, which specifically express the transcription factor forkhead box P3 (Foxp3), are engaged in the maintenance of immunological self-tolerance and homeostasis. By transcriptional start site cluster analysis, we assessed here how genome-wide patterns of DNA methylation or Foxp3 binding sites were associated with Treg-specific gene expression. We found that Treg-specific DNA hypomethylated regions were closely associated with Treg up-regulated transcriptional start site clusters, whereas Foxp3 binding regions had no significant correlation with either up- or down-regulated clusters in nonactivated Treg cells. However, in activated Treg cells, Foxp3 binding regions showed a strong correlation with down-regulated clusters. In accordance with these findings, the above two features of activation-dependent gene regulation in Treg cells tend to occur at different locations in the genome. The results collectively indicate that Treg-specific DNA hypomethylation is instrumental in gene up-regulation in steady state Treg cells, whereas Foxp3 down-regulates the expression of its target genes in activated Treg cells. Thus, the two events seem to play distinct but complementary roles in Treg-specific gene expression.
Related Papers
No related papers found
Powered by citation graph analysis